Jorg van Loosdregt
Wednesday 8 June 2011
Post-translational modification of Foxp3
Promotor: Prof.dr P.J. Coffer and prof.dr B.J. Prakken
Defence: 8 June 2011
The transcription factor Foxp3 is of critical importance for both regulatory T cell (Treg) development and function, and thereby the maintenance of immune homeostasis. Although the transcriptional regulation of Foxp3 has been well investigated, mechanisms of post-translational regulation remain poorly understood. We sought to investigate the molecular mechanisms regulating Foxp3 protein expression and the potential for modulation of transcriptional activity by co-factor association. We report, several novel findings including: a) regulation of Treg functionality by acetylation-mediated Foxp3 protein stabilization, (b) rapid temporal control of Foxp3 protein degradation by Sirtuin-1, (c) Increased Treg mediated suppression through USP7/HAUSP-mediated Foxp3, (d) inhibition of Treg function through inhibition of Foxp3 by canonical Wnt signaling. Manipulation of these mechanisms can provide novel therapeutic strategies to regulate immune responses.